Bleeding diathesis and gastro-duodenal ulcers in inherited cytosolic phospholipase-A2 alpha deficiency

Elena M. Faioni; Cristina Razzari; Aida Zulueta; Eti A. Femia; Lara Fenu; Marco Trinchera; Gian Marco Podda; Mariateresa Pugliano; Francesco Marongiu; Marco Cattaneo

doi:10.1160/th14-04-0352

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2014; 112(06): 1182-1189
DOI: 10.1160/th14-04-0352

Platelets and Blood Cells

Schattauer GmbH

Bleeding diathesis and gastro-duodenal ulcers in inherited cytosolic phospholipase-A2 alpha deficiency

Elena M. Faioni

¹Medicina 3, Azienda Ospedaliera San Paolo and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy

,

Cristina Razzari

¹Medicina 3, Azienda Ospedaliera San Paolo and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy

,

Aida Zulueta

²Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy

,

Eti A. Femia

¹Medicina 3, Azienda Ospedaliera San Paolo and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy

,

Lara Fenu

³Dipartimento di Scienze Mediche Internistiche, Università di Cagliari, Cagliari, Italy

,

Marco Trinchera

⁴Dipartimento di Medicina Clinica e Sperimentale, Università dell’Insubria, Varese; Italy

,

Gian Marco Podda

¹Medicina 3, Azienda Ospedaliera San Paolo and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy

,

Mariateresa Pugliano

¹Medicina 3, Azienda Ospedaliera San Paolo and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy

,

Francesco Marongiu

³Dipartimento di Scienze Mediche Internistiche, Università di Cagliari, Cagliari, Italy

,

Marco Cattaneo

¹Medicina 3, Azienda Ospedaliera San Paolo and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy

› Institutsangaben

Abstract

Summary

Arachidonic acid (AA), when cleaved from phospholipids by cytosolic phospholipase A2 alpha (cPLA2a), generates eicosanoids, with pro-hemostatic, pro-inflammatory, vasoactive and gastro-protective functions. We describe a patient (27-year-old man) and his twin-sister with early-onset bleeding diathesis and recurrent gastro-intestinal (GI) ulcers. Platelet aggregation/δ-granules secretion by collagen was impaired, but normal by AA; serum levels of thromboxane (Tx) B₂ and 12-hydroxyeicosatetraenoic acid, and urinary levels of 11-dehydro- TxB₂ were extremely low. Patients were homozygous for 1723G>C transition in PLA2G4A gene, which changed the codon for Asp575 to His. GI ulcers affected 5/14 heterozygous (< 40 years) and 1/16 wildtype homozygous (> 60 years) family members; none had bleeding diathesis. The proband, his sister and mother also had mildly reduced factor XI levels. Platelet messenger RNA expression did not differ among subjects with different PLA2G4A genotypes. Conversely, platelet cPLA2a was undetectable by Western Blotting in the proband and his sister, and decreased in 1723G>C heterozygous subjects, suggesting that the variant is transcribed, but not translated or translated into an unstable protein. We described a syndromic form of deficiency of cPLA2a , characterised by recurrent GI ulcers and bleeding diathesis, associated with mild inherited deficiency of factor XI. Unlike other reported patients with cPLA2a deficiency, these patients had extremely low levels of platelet TxA₂ biosynthesis.

Keywords

Platelet function disorders - bleeding diathesis - phospholipase A2a deficiency - eicosanoids - gastro-duodenal ulcers

Volltext

Referenzen

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